Hemodynamics Effects of Fludrocortisone on the Pressor Response to Noradrenaline Septic Shock Patients

NCT ID: NCT05001854

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-31
• Study Completion Date: 2024-12-31

Brief Summary

The benefit of low-dose steroids in septic shock is still debated today, especially with mineralocorticoids. Fludrocortisone is a synthetic mineralocorticoid, an analogue of aldosterone, which has shown, in combination with hydrocortisone, a favorable effect on the mortality of septic shock patients with relative adrenal insufficiency. In a previous study in healthy volunteers, we showed for the first time that fludrocortisone at a dose of 400 μg per day significantly improved the pressor response to phenylephrine. These results confirm the observations reported in rats with endotoxin shock, where fludrocortisone was shown to significantly increase blood pressure and contractile response to phenylephrine. These encouraging results argue for a potential vascular beneficial effect of fludrocortisone and need to be confirmed in a population of septic shock patients. In this context, we aimed to evaluate the effect of oral administration of 100 μg every 6 hours of fludrocortisone on vascular responsiveness to noradrenaline in septic shock patients.

Detailed Description

Patients admitted to medical and surgical intensive care units with septic shock who meet the selection criteria may be offered participation in the study. The consent is signed either by the patient or his or her relative/legal representative if he or she is not capable or the patient is included according to the emergency procedure in the absence of a relative. The patient is managed according to the usual procedures for patients in septic shock. After collection of the initial workup and basal measurements, the physician randomizes (=includes) the patient into one of 2 arms : the patient receives either fludrocortisone (400 μg per day), administered in 1 dose of 100 μg every 6 hours, i.e., 2 tablets of 50 μg per dose, or the placebo

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fludrocortisone

100 μg every 6 hours of fludrocortisone per os

A pharmacokinetic study is performed in this arm

Group Type: EXPERIMENTAL

Fludrocortisone

Intervention Type: DRUG

100 μg every 6 hours of fludrocortisone per os

Control

100 μg every 6 hours of placebo per os

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

100 μg every 6 hours of placebo per os

Interventions

Fludrocortisone

100 μg every 6 hours of fludrocortisone per os

Intervention Type: DRUG

Placebo

100 μg every 6 hours of placebo per os

Intervention Type: DRUG

Other Intervention Names

Flucortac

Eligibility Criteria

Inclusion Criteria

• Age > 18 years
• Patient with septic shock for less than 48 hours, defined by the combination of:

• Sepsis defined as organ dysfunction caused by an inappropriate host response to infection (increase in SOFA score of at least 2 points secondary to infection),
• Persistent hypotension requiring vasopressor drugs to maintain mean arterial pressure ≥ 65 mmHg,
• Hemodynamic stability for >30 min with mean arterial pressure ≥ 65 mmHg and noradrenaline dose ≤ 0.5 μg/kg/min,
• Consent signed by the patient, family member, or legal representative or inclusion under emergency procedure,
• Negative to a diagnostic test for SARS-CoV2 less than 72 hours old; the test used must be on the the list published on the Ministry of Solidarity and Health website

• Current treatment with steroids or other treatment that may affect the hypothalamic-pituitary-adrenal axis,
• Anesthetic induction with etomidate within 6 hours prior to randomization given its selective inhibitory effect on 11 β-hydroxylase,
• Known hypersensitivity to fludrocortisone (or any of its excipients), or to tetracosactide (Synacthen®),
• Disturbed gastric emptying (gastric residue > 500 ml) in the absence of an alternative route of administration available (naso-jejunal tube or jejunostomy),
• Pregnant or nursing woman,
• Patient participating in another trial, possibly interfering with the study procedures,
• Person not affiliated to a social security system,
• Known situation of deprivation of freedom (safeguard of justice), guardianship or curatorship,
• Patient with a life expectancy of less than 24 hours.
• Patient with known or suspected SARS-CoV2 pneumonia

Exclusion Criteria

• Patients under court protection will be excluded as soon as the investigator is aware of their status.
• Hemodynamic worsening with noradrenaline dose >1.5 μg/kg/min before evaluation of the primary end point.
• Catecholamine withdrawal before evaluation of the primary end point.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

H.A.C. PHARMA

INDUSTRY

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruno Laviolle, MD, PhD

Role: STUDY_CHAIR

Rennes University Hospital

Harmonie Perrichet, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Locations

Rennes University Hospital - Intensive Care unit

Rennes, Brittany Region, France

Countries

France

Other Identifiers

2020-001430-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

35RC19_8860

Identifier Type: -

Identifier Source: org_study_id